collection of human biospecimens for basic and clinical research into globin variants

Conditions: Alpha and Beta Thalassemia; Sickle Cell Disease; Malaria; Human Physiology

Summary: background: blood disorders like sickle cell disease and malaria affect many people around the world. researchers want to learn more about blood disorders. to do this, they need to collect biological samples from people with blood disorders. they also need to collect samples from healthy people. objective: to collect samples to use for research on blood disorders. eligibility: people ages 18-70 who have blood disorders. healthy volunteers without blood disorders are also needed. design: participants will be screened with a medical history, physical exam, and blood and urine tests. participants will give one or more samples. they will give them over 5 years. they can choose not to give any of the samples: saliva: participants will spit into a tube. they may also have the inside of their mouth swabbed. urine: participants will urinate into a cup. blood and blood waste products: blood will be taken through a needle in the participant s arm. fat samples: an area on the participant s belly or buttock will be numbed. a small cut will be made into the skin and a small piece of fat removed. mucus and cells from the lungs: the participant will be sedated. a flexible tube will be inserted through the nose or mouth into the lung airways. these participants will also have a physical exam, chest x-ray, and heart tests after the procedure.

the physiology unit of the laboratory of malaria and vector research studies the role of globin variants in erythroid and non-erythroid tissues. we hope to better understand the mechanism(s) through which alpha and beta globin variants impact malaria, sickle cell disease, or other diseases involving inflammation or vascular endothelial dysfunction. the collection of human specimens from healthy volunteers and patients with malaria, sickle cell disease, or other diseases involving inflammation or endothelial dysfunction is necessary for the development of laboratory and physiological assays to further basic and clinical research studies. this protocol defines the purposes for which specimens will be collected and establishes general conditions under which sample collection will be performed. development of assays and our research into the roles of alpha and beta globin in normal human physiology, as well as in the pathogenesis of malaria and sickle cell disease, requires laboratory analysis of saliva/buccal swab, urine, blood, blood waste products, adipose tissue, bronchial brushing, and/or bronchoalveolar lavage specimens from human volunteers.

Eligibility criteria:
* participant inclusion criteria: 1. aged 18-70 years. 2. able to provide informed consent. 3. willing to allow biological samples to be stored for future research. 4. willing to provide one or more of the following tissues: saliva, urine, blood, blood waste products, adipose tissue, bronchial brushing, and/or bal samples. 5. willing to allow genetic testing on collected biological samples. participant exclusion criteria: * exclusion criteria for all participants the following exclusion criteria apply to all participants who will provide any of the following samples in-person at the nih cc: saliva, urine, blood, blood waste products, adipose tissue, bronchial brushing, and/or bal samples: 1. pregnancy. 2. positive testing for hepatitis b virus, hepatitis c virus, or hiv (as determined by serum screening tests or relevant viral quantitative studies.) 3. any condition that requires active medical intervention or monitoring to avert serious danger to the individual s health or wellbeing. 4. any condition that, in the opinion of the pi, contraindicates participation in this study. * additional exclusion criteria for individuals giving blood for research 1. hemoglobin \< 10 g/dl for healthy female volunteers, \< 12 g/dl for healthy male volunteers, or \< 6 g/dl for participants with sickle cell disease or other chronic anemias. -additional exclusion criteria for adipose tissue biopsy individuals meeting any of the following criteria will be excluded from undergoing adipose tissue biopsy. if the participant no longer meets any of these criteria at a later time, then they will be allowed to undergo this procedure. 1. currently taking anticoagulation medication. 2. platelets \< 100,000/microl. 3. history of keloid formation (or irregular fibrous tissue formed at the site of a scar or injury). 4. history of adverse reactions to lidocaine or other local anesthetics. 5. any condition that, in the opinion of the pi, contraindicates this procedure. use of aspirin (or acetylsalicylic acid) and nonsteroidal anti-inflammatory drugs (nsaids) are permitted. -additional exclusion criteria for bronchoscopy individuals meeting any of the following criteria will be excluded from undergoing bronchoscopy. if the participant no longer meets any of these criteria at a later time, then they will be allowed to undergo this procedure. 1. prothrombin time (pt) \> 1 second above the upper limit of normal (uln) or international normalized ratio \> 1.3. 2. partial thromboplastin time (ptt) \> 1 second above uln. 3. platelets \< 150,000/microl. 4. currently taking anticoagulation medication. 5. use of aspirin within 2 weeks of the bronchoscopy or nsaids within 2 days of the bronchoscopy. 6. diagnosis of a pulmonary disorder (eg, asthma, chronic bronchitis, cystic fibrosis, or bronchiectasis). 7. respiratory tract infection within the last 4 weeks. 8. history of adverse reactions to systemic and/or local anesthetics that will be used for this procedure. 9. history of cigarette smoking within the past 3 months. 10. history of chronic opioid use. 11. history of drug or alcohol abuse. 12. post-bronchodilator forced expiratory volume in 1 second (fev1) \< 40% of predicted or pre-bronchodilator fev1 \< 35% of predicted. 13. active bronchospasm on physical examination. 14. history of lidocaine allergy. 15. any condition that, in the opinion of the pi, contraindicates this procedure. co-enrollment guidelines: participants may be co-enrolled in other studies. however, the pi must be notified of co-enrollment.

Keywords: assay development malaria sickle cell disease alpha and beta thalassemia natural history